The present invention is concerned with pyrimidine derivatives having HIV (Human Immunodeficiency Virus) replication inhibiting properties. The invention further relates to methods for their preparation and pharmaceutical compositions comprising them. The invention also relates to the use of said compounds for the manufacture of a medicament for the prevention or the treatment of HIV infection.
Compounds structurally related to the present compounds are disclosed in the prior art.
WO 99/50250 and WO 00/27825 disclose substituted aminopyrimidines having HIV replication inhibiting properties.
WO 97/19065 discloses substituted 2-anilinopyrimidines useful as protein kinase inhibitors.
WO 00/62778 concerns cyclic protein tyrosine kinase inhibitors.
WO 98/41512 describes substituted 2-anilinopyrimidines useful as protein kinase inhibitors.
U.S. Pat. No. 5,691,364 describes benzamidine derivatives and their use as anti-coagulants.
WO 00/78731 describes 5-cyano-2-aminopyrimidine derivatives as KDR kinase or FGFr kinase inhibitors useful in the prophylaxis and treatment of diseases associated with angiogenesis.
The compounds of the invention differ from the prior art compounds in structure, pharmacological activity and/or pharmacological potency.
Unexpectedly, it has been found that the compounds of the invention have an improved ability to inhibit the replication of Human Immunodeficiency Virus (HIV), in particular they have an improved ability to inhibit the replication of mutant strains, i.e. strains which have become resistant to art-known drug(s) (drug or multidrug resistant HIV strains).